Should Multilevel Posterior Cervical Fusions Involving C7 Cross the Cervicothoracic Junction? A Systematic Review and Meta-Analysis

Literature Review

Should Multilevel Posterior Cervical Fusions Involving C7 Cross the Cervicothoracic Junction? A Systematic Review and Meta-Analysis Anshit Goyal1,2, Aya Akhras1,4, Waseem Wahood1,2, Mohammed Ali Alvi1,2, Ahmad Nassr3, Mohamad Bydon1,2

Key words C7 - Cervical - Cervicothoracic junction - Crossing - Fusion - Posterior - Reoperation -

Abbreviations and Acronyms ASD: Adjacent segment disease CI: Confidence interval CTJ: Cervicothoracic junction ES: Effect size GRADE: Grading of Recommendations, Assessment, Development and Evaluations OR: Odds ratio PCF: Posterior cervical fusion PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses From the 1Mayo Clinic Neuro-Informatics Laboratory and Departments of 2Neurologic Surgery and 3Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, USA; and 4 Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates To whom correspondence should be addressed: Mohamad Bydon, M.D. [E-mail: [email protected]] Anshit Goyal and Aya Akhras contributed equally to the study. Citation: World Neurosurg. (2019) 127:588-595. https://doi.org/10.1016/j.wneu.2019.03.283

- BACKGROUND:

Current literature remains inconclusive as to whether multilevel posterior cervical fusions (PCFs) involving the C7 vertebra should cross the cervicothoracic junction (CTJ). The objective of this systematic review was to assess the differences in clinical outcomes, fusion, and reoperation rates, between patients undergoing multilevel PCFs ending at C7 and those undergoing PCF crossing the CTJ.

- METHODS:

A systematic review of literature from 4 databases on crossing the CTJ was conducted. Inclusion criteria consisted of 1) patients undergoing multilevel PCF or combined anterior and PCF involving C7, 2) diagnosis for surgery being degenerative disk or deformity.

- RESULTS:

Six studies consisting of 530 patients were included in this review. Two were 1-arm studies and 4 were comparative studies. There were 305 patients (58%) in the noncrossing group and 225 patients (42%) in the crossing group. Among the 3 comparative studies that recorded fusion rate, patients in the crossing group were more likely to achieve fusion (odds ratio, 2.75; 95% confidence interval, 1.61e4.09; P < 0.001) and were less likely to undergo a reoperation (odds ratio, 0.42; 95% confidence interval, 0.25e0.73; P [ 0.002) compared with patients in the noncrossing group. In our indirect analyses, fusion rate and reoperation rate were comparable between the 2 groups (P [ 0.689 and P [ 0.714, respectively).

- CONCLUSIONS:

Our results indicate that based on current evidence, multilevel PCFs that cross the CTJ may have higher fusion rates and lower reoperation rates compared with fusions that stop at C7. These results are important to assist the surgeon in decision making regarding the lower instrumented level when performing a multilevel PCF.

Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.

INTRODUCTION The cervicothoracic junction (CTJ) is a critical surgical landmark because of its distinct anatomic features and has become an area of interest and speculation among surgeons who operate for diseases involving the C6 and/or C7 level.1,2 The biomechanical properties of this region may have a significant role in its instability because of stresses such as trauma, tumors, or degenerative disk disease, among other factors.1 For this reason, it is a commonly encountered area in surgical practice, with many different possible approaches. Anteriorly, the low

588

www.SCIENCEDIRECT.com

cervical or transmanubrial (down to T2) approaches can be used to access the CTJ, particularly for cases involving vertebral bodies.3 However, this strategy carries a high risk of morbidity and complications because of the presence of critical organs and blood vessels in the trajectory of access to the vertebral bodies of interest.4 Alternatively, there are posterior approaches to access the cervicothoracic junction. These approaches frequently require instrumentation or fusion to overcome instability.3 Posterior cervical fusion (PCF) has become more popular over the years for lower cervical diseases5,6; however, the debate of whether to fuse or not depends on numerous factors, such as patient age,

preoperative sagittal alignment, diagnosis, and the number of levels involved.7 Regarding fusion of the posterior cervical spine, absolute indications include postlaminectomy of a kyphotic spine or a spine with deformity, and bilateral facetectomy. Controversial indications include postlaminectomy of straightened spine or a spine with axial pain.8 There is also speculation regarding increased risk of adjacent segment degeneration with multilevel (>1 level) fusions ending at C7, because of the biomechanical transition to a rigid thoracic spine.9 Some studies have advocated for bridging the CTJ in multilevel fusions to avoid such complications.10,11 The literature is inconclusive as to whether patients

WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.283

LITERATURE REVIEW ANSHIT GOYAL ET AL.

CROSSING VS NOT CROSSING THE CTJ

Figure 1. Flow diagram showing the literature review, search strategy, and selection process. ACDF, anterior cervical

requiring fusion up to C7 should also fuse across the CTJ into the thoracic spine (T1T2). The objective of our systematic review is to assess the differences in clinical outcomes, particularly rate of fusion and reoperations, between patients undergoing multilevel PCFs up to C7 (not crossing CTJ), and those up to T1-T2 (crossing CTJ).

METHODS Search Strategy This systematic review was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.12 The study question was

decompression and fusion; CTJ, cervicothoracic junction.

structured around the PICO format: do patients undergoing multilevel posterior or combined anterior and PCF involving C7 (Population), who receive fusion crossing the CTJ (Intervention) compared with those who do not (Comparator) have superior surgical outcomes (Outcome)? A systematic review of 4 electronic databases (Ovid MEDLINE, Ovid Embase, Ovid Central, and Scopus) was conducted by a master’s level librarian from their dates of inception until June 22, 2018. The search strategy is presented in Supplementary Table 1. The identified articles were independently assessed against the inclusion and exclusion criteria by 2 study investigators. Figure 1 shows the PRISMA

WORLD NEUROSURGERY 127: 588-595, JULY 2019

flowchart for search methodology. No institutional review board approval or patient consent was required for this meta-analysis, because only published data were used. Selection Criteria Inclusion criteria consisted of studies with 1) patients undergoing multilevel PCF or combined anterior and PCF involving C7, 2) primary diagnosis of degenerative cervical spine disease, and 3) full-text articles. Studies were excluded if 1) indication for surgery was fracture, tumor, trauma, or infection, 2) the primary procedure was arthroplasty, laminoplasty, or corpectomy, 3) patients were undergoing single-level

www.journals.elsevier.com/world-neurosurgery

589

LITERATURE REVIEW ANSHIT GOYAL ET AL.

CROSSING VS NOT CROSSING THE CTJ

Table 1. Demographics and Characteristics of the Studies

Reference Hart et al., 200813

Study Design

Country

United States Retrospective

Mean Females Age (%) (years)

Sample Size

Crossing vs. Not Crossing

Follow-Up Time (Mean)

13

Crossing

54

56

Minimum 2 years

Dynamic radiographs or computed tomography scans at 2 years follow-up

Fusion Assessment

Demura et al., 201314

Japan

Retrospective

15

Not crossing

47

52

71 months

Multiplanar reconstruction computed tomography at last follow-up

Osterhoff et al., 201715

Germany

Retrospective

74

Crossing vs. not crossing

39

64

37 months

Not applicable

Schroeder et al., 201616 United States Retrospective

189

Crossing vs. not crossing

47

61.9

51.6 months

Radiography at 1 year

Truumees et al., 201817

United States Retrospective

177

Crossing vs. not crossing

48

59.5

Minimum 2 yrs

Radiography at 2 year

Bechara et al., 201218

United States

62

Crossing vs. not crossing

56

58.8

7.49 months

Radiography at last follow-up

Prospective

spinal fusion, and 4) case reports, reviews, editorials, and conference abstracts were excluded. For studies from the same institution and author, only the most recent and updated reports were included. To ensure the inclusion of all relevant studies, a manual search of reference lists was conducted. Data Extraction The following data were independently extracted by 2 study investigators: sample size, demographics such as age, sex, body mass index, length of follow-up, and surgically pertinent variables such as approach (posterior or combined anterior and posterior) and vertebral levels. Primary Outcomes. The primary outcomes assessed included rate of fusion, complications, and reoperations. The methodology to assess fusion was variable across studies (Table 1). Secondary Outcomes. Secondary outcomes included operative duration and estimated blood loss. Frequency of adjacent segment disease (ASD), change in visual analog scale score and Oswestry Disability Index were also important outcomes of interest; however, they were not consistently reported. Meta-Analysis Direct and indirect meta-analyses were conducted for fusion rate and reoperations. In the case of direct meta-analysis,

590

www.SCIENCEDIRECT.com

outcomes were summarized using odds ratios (ORs) with corresponding 95% confidence intervals (CIs). With our indirect meta-analysis, outcomes were summarized with pooled proportions of events (effect size [ES]). CIs were calculated using the Wilson Score method.19 FreemanTukey transformation20 was used to include studies with zero event rate and stabilize variance. The DerSimonian and Laird approach21 for random-effects model was used to account for high variability between studies. P < 0.05 was considered statistically significant. All analyses were performed using Stata (StataCorp. 2015. Stata Statistical Software: Release 14 [StataCorp LLC, College Station, Texas, USA]). Evidence Quality and Publication Bias Assessment Each study was evaluated using the Newcastle-Ottawa Scale22 and GRADE (Grading of Recommendations, Assessment, Development and Evaluations) criteria.23 Publication bias was evaluated by generating funnel plots and examining them for any obvious visual asymmetry.24 RESULTS Literature Search Our search yielded 2850 studies, found through a comprehensive database search. After the removal of 32 duplicative articles,

288 abstracts, and applying the inclusion/ exclusion criteria to the remaining articles, 31 articles underwent full-text analysis. Six articles13-18 were included in this review. Two studies reported outcomes for patients undergoing multilevel PCF crossing the CTJ only, whereas 4 studies compared outcomes for patients undergoing multilevel PCF crossing the CTJ with those who did not cross the CTJ. Figure 1 shows the PRISMA search strategy. Demographics A total of 530 patients were included across 6 studies. Patients were divided into 2 groups: not crossing the CTJ, with fusion up to C7 caudally; and crossing the CTJ, with the caudal level of instrumentation at T1 or T2. There were 305 patients (58%) in the noncrossing group, and 225 patients (42%) in the crossing group. All patients underwent either multilevel PCF or combined anterior and posterior multilevel cervical fusion. Mean age ranged from 51 to 63 years in the noncrossing group, and from 56 to 65 years in the crossing group. The proportion of females was 51% and 45.8%, respectively. Levels operated on ranged from C1-T2. All surgeries included posterior fusion. Characteristics of included studies are summarized in Table 1. Direct Comparison Fusion Rate. Fusion rate was compared among the 3 studies (n ¼ 428) that directly

WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.283

LITERATURE REVIEW ANSHIT GOYAL ET AL.

Figure 2. (A) Forest plot directly comparing fusion rate between crossing and not crossing the cervicothoracic junction. (B) Forest plot directly comparing reoperation rate between crossing and

WORLD NEUROSURGERY 127: 588-595, JULY 2019

CROSSING VS NOT CROSSING THE CTJ

not crossing the cervicothoracic junction. CI, confidence interval; OR, odds ratio.

www.journals.elsevier.com/world-neurosurgery

591

LITERATURE REVIEW ANSHIT GOYAL ET AL.

CROSSING VS NOT CROSSING THE CTJ

Figure 3. (A) Forest plot indirectly comparing fusion rate between crossing and not crossing the cervicothoracic junction. (B) Forest plot indirectly

592

www.SCIENCEDIRECT.com

comparing reoperation rate between crossing and not crossing the cervicothoracic junction. CI, confidence interval. ES, effect size.

WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.283

LITERATURE REVIEW ANSHIT GOYAL ET AL.

CROSSING VS NOT CROSSING THE CTJ

Table 2. GRADE Assessment of Quality of Evidence Outcome

Number of Number of Other Studies Patients Inconsistency Indirectness Imprecision Consideration

Relative Effect (95% Confidence Interval)

Confidence in Effect Estimates (GRADE)

Fusion rate (not crossing)

4

247

Serious

Not serious

Not serious

Not serious

0.89 (0.68e1.00)

Moderate

Reoperations (not crossing)

5

305

Serious

Not serious

Not serious

Not serious

0.15 (0.03e0.34)

Moderate

Fusion rate (crossing)

4

209

Serious

Not serious

Not serious

Not serious

0.93 (0.84e0.99)

Moderate

Reoperations (crossing)

5

225

Serious

Not serious

Not serious

Not serious

0.11 (0.03e0.23)

Moderate

compared crossing with not crossing the CTJ. Successful fusion was observed in 349/428 patients (82%). All studies assessed fusion using radiography. From this comparison, we found that fusion rates are more likely to occur with crossing the CTJ than not crossing (OR, 2.75; 95% CI, 1.61e4.09; P < 0.001). These results are shown as a forest plot in Figure 2A. Reoperation Rate. Reoperation rates were compared among 4 studies (502 patients) that directly compared crossing the CTJ with not crossing. The overall reoperation rate was 17% (n ¼ 84). Crossing the CTJ was associated with lower odds of revision surgery (OR, 0.42; 95% CI, 0.25e0.73; P ¼ 0.002). These results are shown as a forest plot in Figure 2B. Indirect Comparison Fusion Rate. Fusion rate was reported in 5 studies (n ¼ 456), with 193/247 patients (78%) in the noncrossing group and 184/ 209 patients (88%) in the crossing group who had a successful fusion. Two studies assessed fusion with computed tomography, whereas 3 used radiography. There was no significant difference (P ¼ 0.689) in mean fusion rate between crossing (ES, 0.95; 95% CI, 0.87e1.00) and not crossing the CTJ (ES, 0.89; 95% CI, 0.68e1.00). These results are shown as a forest plot in Figure 3A. Reoperation Rate. The rate of reoperation was consistently reported throughout the 6 studies (n ¼ 530). A total of 60 patients (11%) underwent a reoperation in the noncrossing group, compared with 48 patients (9%) in the crossing group. The overall incidence of reoperation between the 2 groups was comparable (P ¼ 0.714)

with a rate of 0.11 (95% CI, 0.03e0.23) for the crossing group and 0.15 (95% CI, 0.03e0.34) in the noncrossing group. These results are further assessed in Figure 3B. The most common reason for reoperation among patients with fusion up to C7 was ASD (n ¼ 20), followed by wound complication (n ¼ 5) and pseudarthrosis (n ¼ 5). In contrast, the reasons for reoperation among patients receiving a fusion crossing the CTJ included wound complications (n ¼ 2), ASD (n ¼ 1), cerebrospinal fluid leak (n ¼ 1), early hardware failure (n ¼ 1), pseudarthrosis (n ¼ 1), and trauma (n ¼ 1). These are summarized in Supplementary Table 2. Quality Assessment Study Quality. The Newcastle-Ottawa Scale was used to assess study quality. Based on its guidelines, overall, the quality of the studies was high, with scores ranging from 5 to 6. All studies included a star for representativeness of cohort, ascertainment of exposure, outcome of interest, assessment of outcome, and adequate duration of follow-up. The Newcastle-Ottawa Scale results are shown in Supplementary Table 3. Strength of Evidence. Based on GRADE approach, confidence in estimates was found to be moderate for fusion rate and reoperation. GRADE assessment is shown in Table 2. Publication Bias. To assess for publication bias, we generated funnel plots. No obvious visual asymmetry could be ascertained. Funnel plots are presented in Supplementary Figures 1e4.

WORLD NEUROSURGERY 127: 588-595, JULY 2019

DISCUSSION This systematic review and meta-analysis sought to compare the differences in outcomes of multilevel PCFs that cross the CTJ with those that do not cross the CTJ. We also included an indirect comparison in addition to analyzing studies that directly compared the 2 approaches. Results of our direct comparison showed more successful fusions and fewer reoperations in multilevel PCFs crossing the CTJ. The indirect assessment pointed to a similar trend, although the results were not statistically significant. There has been little evidence on complications after posterior fusion surgeries crossing the CTJ. Regarding multilevel PCFs, Osterhoff et al.15 found that more patients with cervical fusions ending at C7 had clinically relevant disease, occurring below the lowest instrumented vertebra, thus favoring crossing the CTJ. Schroeder et al.16 sought to determine differences in revision rates between patients undergoing multilevel PCFs ending at C7 and those extending into the thoracic spine. The overall revision rate was 27.8%, with a significant difference between the groups. These investigators found that revision rates were higher in the C7 group and reported that 15% of revision surgeries were caused by ASD in the C7 group, compared with none in the T1 group. Truumees et al.17 conducted a multicenter comparison of radiographic and clinical data of patients undergoing multilevel PCFs in those crossing versus not crossing the CTJ. These investigators found that extending the fusion into the thoracic spine leads to a lower rate of nonunion, whereas not crossing the CTJ

www.journals.elsevier.com/world-neurosurgery

593

LITERATURE REVIEW ANSHIT GOYAL ET AL.

has benefits such as lower blood loss, shorter operative, and length of hospital stay. Bechara et al.18 concluded that extending the fusion to T1 resulted in a loss of range of motion, but no difference in time to healing and functional disability was observed with not crossing the CTJ. Hart et al.13 concluded that perioperative complications of anterior cervical decompression and fusion and PCF crossing the CTJ are frequent but do not affect clinical outcomes, and reported no ASD. Demura et al.14 did not cross the CTJ and reported a 100% fusion rate, with an 11% rate of ASD requiring reoperation. Although there are many studies evaluating outcomes and complication rates after anterior cervical fusions,25-29 corresponding literature for PCF is sparse. The debate regarding crossing versus not crossing the CTJ has been ongoing in recent years. With increasing rates of PCF surgery, it is crucial to address this topic more comprehensively. Crossing the CTJ requires a careful evaluation of many factors. The patient’s age, smoking status, sagittal alignment, and other biomechanical measurements should be taken into consideration. Because the CTJ is such a biomechanically unique region of the spine,1 more large-scale prospective studies are needed to confirm whether fusing across the CTJ is beneficial to avoid instability and risk of ASD across the C7T1 level. Strengths and Limitations We present in this study a systematic review and meta-analysis of the literature regarding the differences in clinical outcomes between crossing and not crossing the CTJ. The meta-analysis allowed for the detection of significant differences in reoperations and fusion rates between multilevel PCFs crossing the CTJ versus not crossing the CTJ. We conducted a thorough literature review, with accompanying inclusion/exclusion criteria as dictated by the PRISMA guidelines and conducted a robust quality assessment using the Newcastle-Ottawa Scale and GRADE guidelines. Nonetheless, our study bears some limitations. First, we could identify only a few studies that adequately answered our research question, which may compromise the external

594

www.SCIENCEDIRECT.com

CROSSING VS NOT CROSSING THE CTJ

validity of our results. Second, we conducted an indirect analysis to include more studies, and thus, conclusions from these results should be inferred with caution. Third, although one of the inclusion criteria was multilevel PCF, included studies were heterogeneous in surgical techniques; this could affect the outcomes analyzed. Fourth, in one of our studies, all patients included had athetoid cerebral palsy, a movement disorder caused by damaged to the basal ganglia or cerebellum.14 Although this factor did not affect the outcome of interest, it does decrease external validity. Fifth, the specific operative technique used for either type of these procedures may be different depending on the experience and preference of the operating surgeon. For instance, a cadaveric study by Kretzer et al. showed that for thoracic constructs stopping at T-1, the posterior supraspinous ligament/interspinous ligament complex plays a vital role in CTJ stability, and that disruption of the posterior tension band may significantly destabilize the CTJ in flexion/extension, which may then clinically manifest as proximal junction kyphosis.11 On the other hand, for fusions ending at C7, Hong et al.30 showed that C7 pedicle screws may provide a more stable construct for C6-C7 posterior fixation, compared with C7 laminar screw fixation; however, the latter may be associated with higher range of motion in lateral bending and higher load-sharing capability compared with lateral mass screw. Sixth, we could not account for potential confounders such as age, smoking status, and osteoporosis because of the limited number of studies and lack of individual level patient data. Seventh, outcomes such as the visual analog scale and Oswestry Disability Index could not be analyzed because they were reported in only 2 studies. Many outcome variables were not consistently reported throughout the studies. ASD is a common complication of fusion surgeries that was not consistently reported.30,31 CONCLUSIONS In a systematic review of the literature to assess the differences in clinical outcomes of multilevel PCFs stopping at C7

(not crossing CTJ) compared with those extending to T1-T2 (crossing CTJ), we found that multilevel PCFs up to T1-T2 (crossing CTJ) have higher fusion rates and lower reoperation rates. Our metaanalysis provided some insight into the differences in clinical outcomes among the 2 interventions. We believe that this meta-analysis will aid surgeons when deciding when to fuse across the CTJ, because limited evidence about this matter has been disseminated thus far. Future prospective studies will validate the findings of this study and provide insight into differences in other clinically important outcomes such as readmissions, complications, and functional outcomes between the 2 groups. ACKNOWLEDGMENTS We acknowledge the efforts of Patricia J. Erwin, M.L.S for her contribution in the review of the literature. REFERENCES 1. An HS, Vaccaro A, Cotler JM, Lin S. Spinal disorders at the cervicothoracic junction. Spine. 1994; 19:2557-2564. 2. Wang VY, Chou D. The cervicothoracic junction. Neurosurg Clin North Am. 2007;18:365-371. 3. Chapman JR, Anderson PA, Pepin C, Toomey S, Newell DW, Grady MS. Posterior instrumentation of the unstable cervicothoracic spine. J Neurosurg. 1996;84:552-558. 4. Cheung JP, Luk KD. Complications of anterior and posterior cervical spine surgery. Asian Spine J. 2016;10:385. 5. Marquez-Lara A, Nandyala SV, Fineberg SJ, Singh K. Current trends in demographics, practice, and in-hospital outcomes in cervical spine surgery: a national database analysis between 2002 and 2011. Spine (Phila Pa 1976). 2014;39: 476-481. 6. Myhre SL, Buser Z, Meisel HJ, et al. Trends and cost of posterior cervical fusions with and without recombinant human bone morphogenetic protein-2 in the US Medicare population. Glob Spine J. 2017;7:334-342. 7. Lapsiwala S, Benzel E. Surgical management of cervical myelopathy dealing with the cervicale thoracic junction. Spine J. 2006;6:S268-S273. 8. Bambakidis NC, Feiz-Erfan I, Klopfenstein JD, Sonntag VKH. Indications for surgical fusion of the cervical and lumbar motion segment. Spine. 2005;30(16 suppl):S2-S6. 9. Lawrence BD, Hilibrand AS, Brodt ED, Dettori JR, Brodke DS. Predicting the risk of adjacent segment pathology in the cervical spine. Spine. 2012;37:S52-S64.

WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.283

LITERATURE REVIEW ANSHIT GOYAL ET AL.

CROSSING VS NOT CROSSING THE CTJ

10. Cheng I, Sundberg EB, Iezza A, Lindsey DP, Riew KD. Biomechanical determination of distal level for fusions across the cervicothoracic junction. Glob Spine J. 2015;5:282-286.

18. Bechara BP, Bell KM, Hartman RA, Lee JY, Kang JD, Donaldson WF. In vivo analysis of cervical range of motion after 4- and 5-level subaxial cervical spine fusion. Spine. 2012;37:E23-E29.

11. Kretzer RM, Hu N, Umekoji H, et al. The effect of spinal instrumentation on kinematics at the cervicothoracic junction: emphasis on soft-tissue response in an in vitro human cadaveric model. J Neurosurg Spine. 2010;13:435-442.

19. Wilson EB. Probable inference, the law of succession, and statistical inference. J Am Stat Assoc. 1927;22:209.

12. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting Items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097. 13. Hart RA, Tatsumi RL, Hiratzka JR, Yoo JU. Perioperative complications of combined anterior and posterior cervical decompression and fusion crossing the cervico-thoracic junction. Spine. 2008; 33:2887-2891. 14. Demura S, Murakami H, Kawahara N, Kato S, Yoshioka K, Tsuchiya H. Laminoplasty and pedicle screw fixation for cervical myelopathy associated with athetoid cerebral palsy: minimum 5-year follow-up. Spine. 2013;38:1764-1769. 15. Osterhoff G, Ryang Y-M, von Oelhafen J, Meyer B, Ringel F. Posterior multilevel instrumentation of the lower cervical spine: is bridging the cervicothoracic junction necessary? World Neurosurg. 2017; 103:419-423. 16. Schroeder GD, Kepler CK, Kurd MF, et al. Is it necessary to extend a multilevel posterior cervical decompression and fusion to the upper thoracic spine? Spine. 2016;41:1845-1849. 17. Truumees E, Singh D, Geck MJ, Stokes JK. Should long-segment cervical fusions be routinely carried into the thoracic spine? A multicenter analysis. Spine J. 2018;18:782-787.

20. Freeman MF, Tukey JW. Transformations related to the angular and the square root. Ann Math Stat. 1950;21:607-611. 21. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177-188.

previous anterior cervical arthrodesis. J Bone Joint Surg Am. 1999;81:519-528. 28. Louie PK, Presciutti SM, Iantorno SE, et al. There is no increased risk of adjacent segment disease at the cervicothoracic junction following an anterior cervical discectomy and fusion to C7. Spine J. 2017; 17:1264-1271. 29. Elsawaf A, Mastronardi L, Roperto R, Bozzao A, Caroli M, Ferrante L. Effect of cervical dynamics on adjacent segment degeneration after anterior cervical fusion with cages. Neurosurg Rev. 2009;32: 215-224 [discussion: 224].

22. Wells GA, Shea B, O’Connell D, et al. Newcastle-Ottawa Quality Assessment Scale, Cohort Studies; 2014. Available at: http://www.ohri.ca/programs/ Accessed clinical_epidemiology/oxford.asp. January 26, 2019.

30. Ahn S-S, Paik H-K, Chin D-K, Kim S-H, Kim DW, Ku M-G. The fate of adjacent segments after anterior cervical discectomy and fusion: the influence of an anterior plate system. World Neurosurg. 2016;89:42-50.

23. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64:383-394.

31. Litrico S, Lonjon N, Riouallon G, et al. Adjacent segment disease after anterior cervical interbody fusion: a multicenter retrospective study of 288 patients with long-term follow-up. Orthop Traumatol Surg Res. 2014;100(6 suppl):S305-S309.

24. Sterne JAC, Egger M. Funnel plots for detecting bias in meta-analysis. J Clin Epidemiol. 2001;54: 1046-1055. 25. Carrier CS, Bono CM, Lebl DR. Evidence-based analysis of adjacent segment degeneration and disease after ACDF: a systematic review. Spine J. 2013;13:1370-1378. 26. Ishihara H, Kanamori M, Kawaguchi Y, Nakamura H, Kimura T. Adjacent segment disease after anterior cervical interbody fusion. Spine J. 2004;4:624-628. 27. Hilibrand AS, Carlson GD, Palumbo MA, Jones PK, Bohlman HH. Radiculopathy and myelopathy at segments adjacent to the site of a

WORLD NEUROSURGERY 127: 588-595, JULY 2019

Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 16 February 2019; accepted 28 March 2019 Citation: World Neurosurg. (2019) 127:588-595. https://doi.org/10.1016/j.wneu.2019.03.283 Journal homepage: www.journals.elsevier.com/worldneurosurgery Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2019 Elsevier Inc. All rights reserved.

www.journals.elsevier.com/world-neurosurgery

595

LITERATURE REVIEW ANSHIT GOYAL ET AL.

CROSSING VS NOT CROSSING THE CTJ

APPENDIX CENTRAL- 4 Embase <1988 to 2018 Week 26>

Supplementary Table 1. Search Strategy. Ovid MEDLINE Epub Ahead of Print, In-Process and Other NonIndexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE <1946 to Present> Search History Sorted by Search Number Ascending Number

Searches

Results

Type

1

spinal fusion.mp. or Spinal Fusion/

24,244

Advanced

2

exp intervertebral disc degeneration/or exp intervertebral disc displacement/or exp spinal stenosis/or exp spondylitis/or exp spondylosis/

60,858

Advanced

3

(diskectom* or discectom*).mp. [mp¼title, abstract, original title, name of substance word, subject heading word, floating sub-heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]

7999

Advanced

4

(c7 and t1).mp. [mp¼title, abstract, original title, name of substance word, subject heading word, floating sub-heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]

1230

Advanced

5

1 or 2 or 3

81,994

Advanced

6

4 and 5

254

Advanced

7

(cervicothoracic or "cervico thoracic").mp. [mp¼title, abstract, original title, name of substance word, subject heading word, floating sub-heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]

2194

Advanced

8

5 and 7

280

Advanced

9

6 or 8

484

Advanced

10

9 and (outcome* or complication* or reoperation or "re-operation" or revis*).mp. [mp¼title, abstract, original title, name of substance word, subject heading word, floating sub-heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]

336

Advanced

11

limit 10 to english language

304

Advanced

12

remove duplicates from 11

304

Advanced

13

12 not (case reports.pt. or case.jw.)

197

595.E1

www.SCIENCEDIRECT.com

WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.283

LITERATURE REVIEW ANSHIT GOYAL ET AL.

CROSSING VS NOT CROSSING THE CTJ

Search History Sorted By Search Number Ascending Number 1 2

Searches

Results

exp discectomy/or exp spine fusion/

Type

25,209 Advanced

(c7 and t1).mp. [mp¼title, abstract, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade 1682 Advanced name, keyword, floating subheading word, candidate term word]

3

1 and 2

150

Advanced

4

exp intervertebral disk disease/

5

exp intervertebral disk disease/su and 2

28,254 Advanced

6

cervical spine/and thoracic spine/

7

(1 or 4) and 6

247

Advanced

8

3 or 5 or 7

402

Advanced

33

Advanced

1978 Advanced

9

..l/8 lg¼en and hu¼y

370

Advanced

10

9 not case report/

270

Advanced

11

remove duplicates from 10

268

Advanced

12

11 and (followup/or outcome*.mp. or complicat*.mp. or reoperat*.mp. or revis*.mp.) [mp¼title, abstract, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword, floating subheading word, candidate term word]

173

Advanced

13

(1 or exp intervertebral disk disease/su) and (cervicothoracic or "cervico thoracic").mp. [mp¼title, abstract, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword, floating subheading word, candidate term word]

186

Advanced

14

13 not 12

151

Advanced

15

14 and (followup/or outcome*.mp. or complicat*.mp. or reoperat*.mp. or revis*.mp.)

111

Advanced

16

15 not case report/

54

Scopus (TITLE-ABS-KEY ( ( cervicothoracic OR "cervico thoracic" OR ( c7 AND t1) ) AND fusion) AND TITLE-ABS-KEY (( outcome* OR risk* OR complicat* OR reoperat* OR revis* OR "re-operat*" OR follow* OR adverse*) )) 385

WORLD NEUROSURGERY 127: 588-595, JULY 2019

www.journals.elsevier.com/world-neurosurgery

595.E2

LITERATURE REVIEW ANSHIT GOYAL ET AL.

CROSSING VS NOT CROSSING THE CTJ

Supplementary Table 2. Reasons for Reoperations Reasons for Reoperations Reference

Crossing Cervicothoracic Junction

Not Crossing Cervicothoracic Junction

Not listed

Not available

Not available

1 worsening myelopathy caused by C1-C2 instability. Revision ¼ occipitocervical fusion 1 distal junctional instability C7-T1 - revision ¼ fusion extension to thoracic spine

13

Hart et al., 2008

14

Demura et al., 2013

Osterhoff et al., 201715 1 symptomatic lower adjacent segment disease or implant failure 1 cerebrospinal fluid leak

18 symptomatic lower adjacent segment disease or caudal implant failure 2 surgical site infection

Schroeder et al., 201616

1 Early hardware failure 1 Acute wound complication 1 Late infection 1 Nonunion 1 Trauma/fracture 1 Other 13 Not listed

2 Adjacent level disease 3 Acute wound complication 5 Nonunion 3 Other 17 Not listed

Truumees et al., 201817

Not listed

Not listed

No reoperations

No reoperations

18

Bechara et al., 2012

Supplementary Table 3. Assessment of the Quality of Included Studies According to the Newcastle-Ottawa Quality Assessment Scale Quality Assessment Criteria Representativeness of Cohort

Reference

Ascertainment of Exposure

Outcome of Interest

Assessment of Outcome

Adequate Duration of Follow-Up

Adequate Follow-Up of Cohort

*

*

*

*

*

*

*

*

Cervical spinal fusion crossing the cervicothoracic junction Hart et al., 200813

*

*

Cervical spinal fusion not crossing the cervicothoracic junction Demura et al., 201314

*y

*

Cervical spinal fusion crossing vs. not crossing the cervicothoracic junction Osterhoff et al, 201715

*

*

*

*z

*

*

Schroeder et al., 201616

*

*

*

*

*

—x

Truumees et al., 201817

*

*

*

*

*

*

Bechara et al., 201218

*

*

*

*

*

*

yPatients had athetoid cerebral palsy; however, this did not affect the surgical outcomes. zFull radiographic follow-up was only 70%. xRadiographic follow-up adequate for measurement was present in only 69 patients.

595.E3

www.SCIENCEDIRECT.com

WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.283

LITERATURE REVIEW ANSHIT GOYAL ET AL.

CROSSING VS NOT CROSSING THE CTJ

Supplementary Figure 1. Funnel plot for direct comparison of fusion rate between crossing and not crossing the cervicothoracic junction.

Supplementary Figure 2. Funnel plot for direct comparison of reoperation rate between crossing and not crossing the cervicothoracic junction.

WORLD NEUROSURGERY 127: 588-595, JULY 2019

www.journals.elsevier.com/world-neurosurgery

595.E4

LITERATURE REVIEW ANSHIT GOYAL ET AL.

CROSSING VS NOT CROSSING THE CTJ

Supplementary Figure 3. Funnel plot for indirect comparison of fusion rate between crossing and not crossing the cervicothoracic junction.

Supplementary Figure 4. Funnel plot for indirect comparison of reoperation rate between crossing and not crossing the cervicothoracic junction.

595.E5

www.SCIENCEDIRECT.com

WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2019.03.283